The field of the invention relates generally to pharmaceutical dosage unit tablets containing a drug and excipients, and processes for forming the tablets.
In some aspects of the disclosure, the drug is an inhibitor of the mitogen-activated protein kinase enzymes MEK1 and MEK2. Such MEK inhibitors are indicated for the treatment of patients with unresectable or metastatic melanoma with the BRAFV600 mutations. In some particular aspects of the disclosure, the drug is cobimetinib ([3,4-Difluoro-2-(2-fluoro-4-iodoanilino)phenyl]{3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl} methanone) and salts thereof. In yet other particular aspects of the disclosure, the drug is crystalline hemifumarate salt of (S)-[3,4-Difluoro-2-(2-fluoro-4-iodoanilino)phenyl]{3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl} methanone) designated as Form A.
Immediate-release compressed tablets (e.g., caplets) are an effective form for delivering pharmaceutically active drugs. Compressed tablets often involve multiple steps in order to incorporate pharmaceutically active agents into the form since only certain materials (excipients) may be suitable for compression. The drug active and excipients must have the correct compression characteristics such as flow and compressibility in order to maintain operability on a tablet press, retain shape and form without breakage, and dissolve within an appropriate timeframe in the gastrointestinal tract.
Problematically, some combinations of drugs, fillers and disintegration agents (to impart rapid release properties) have poor compression characteristics thereby presenting mechanical strength and dissolution issues for tablets prepared by dry granulation and tablet compression methods.
A need therefore exists for improved tablet compositions containing a drug, a filler and a disintegration agent and related preparation methods that allow for tablets having both (1) sufficient hardness to resist breakage, chipping and abrasion and (2) adequate dissolution and disintegration characteristics required for immediate-release tablets.